Background. Loss-of-function mutations in the filaggrin (FLG) gene were identified as a major risk factor for atopic eczema.

No abstract

The regulation of IL-4RA gene expression is complex and probably influenced by both genetic and environmental factors, such as farming exposures, which could provide the counterbalance to atopy.

A b s t r a c t Introduction: Atopic dermatitis is a chronic inflammatory skin disease with a strong genetic basis. Recent GWASs have identified a single nucleotide polymorphism on chromosome 11q13.5 (rs7927894) as novel susceptibility loci of atopic dermatitis. Aim: To evaluate the association of this genetic variant with atopic dermatitis and to investigate its possible interaction with filaggrin null mutations in children population. Material and methods: One hundred eighty-eight children less than 2 years old were screened for the variant of allele of rs7927894 on chromosome 11q13.5 and for the 4 most prevalent filaggrin mutations. The variant of allele of rs7927894 and all filaggrin mutations were genotyped by real-time PCR assays with subsequent melting curve analysis using SimpleProbe ® probes. Results: The allele of rs7927894[T] was associated with a significantly increased risk of atopic dermatitis (OR = 2.21; 95% CI: 1.14-4.28; p = 0.015). Both allergic and non-allergic patient groups had rs7927894[T] allele significantly more frequently than the control group, however, the frequency of alleles did not differ in these two groups. Interestingly, when rs7927894 variant and filaggrin mutations were considered together, the risk of atopic dermatitis was the most increased in the subjects who combined both rs7927894[T] allele and filaggrin mutations (OR = 16.41; p = 0.003). Conclusions:Our results indicate that the rs7927894 variant on chromosome 11q13.5 may play a role in the development of atopic dermatitis, but this effect seems to be independent of allergic sensitization and of the wellestablished filaggrin risk alleles, but may be modulated by gene-gene interactions.

Boznański A. Genetic polymorphisms in pattern recognition receptors are associated with allergic diseases through gene-gene interactions.